Biomimetic Nano-Degrader Based CD47-SIRPα Immune Checkpoint Inhibition Promotes Macrophage Efferocytosis for Cardiac Repair.

ABSTRACT: CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity. RLP would bind with SIRPα and induce its lysosomal degradation through receptor-mediated endo

SUBMITTER: Gao J 

PROVIDER: S-EPMC11200091 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature